|
|
||||||||
J. Biol. Chem., Vol. 276, Issue 23, 19845-19854, June 8, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Among the few characterized genes that have
products involved in the pathogenicity of Mycobacterium
tuberculosis, the etiological agent of tuberculosis, are those of
the phthiocerol dimycocerosate (DIM) locus. Genes involved in
biosynthesis of these compounds are grouped on a 50-kilobase
fragment of the chromosome containing 13 genes. Analysis of mRNA
produced from this 50-kilobase fragment in the wild type strain showed
that this region is subdivided into three transcriptional units.
Biochemical characterization of five mutants with transposon insertions
in this region demonstrated that (i) the complete DIM molecules are
synthesized in the cytoplasm of M. tuberculosis before
being translocated into the cell wall; (ii) the genes
fadD26 and fadD28 are directly involved in
their biosynthesis; and (iii) both the drrC and
mmpL7 genes are necessary for the proper localization of
DIMs. Insertional mutants unable to synthesize or translocate DIMs
exhibit higher cell wall permeability and are more sensitive to
detergent than the wild type strain, indicating for the first time
that, in addition to being important virulence factors, extractable
lipids of M. tuberculosis play a role in the cell envelope
architecture and permeability. This function may represent one of the
molecular mechanisms by which DIMs are involved in the virulence of
M. tuberculosis.
Analysis of the Phthiocerol Dimycocerosate Locus of
Mycobacterium tuberculosis
EVIDENCE THAT THIS LIPID IS INVOLVED IN THE CELL WALL
PERMEABILITY BARRIER*
§,
,
,
,
Unité de Génétique
Mycobactérienne, Institut Pasteur, 25 rue du Dr. Roux, 75725 Paris Cedex 15, France and the ¶ Institut de Pharmacologie et
Biologie Structurale, UMR 5089 (UPS/CNRS), 205 route de Narbonne,
31077 Toulouse Cedex, France
*
This work was supported by CNRS, the Institut Pasteur, the
Ministère de l'Education Nationale de la Recherche et de la
Technologie (Program de Recherche Fondamentale en Microbiologie et
Maladies Infectieuses et Parasitaires), and European Commission Grant
QLK2-CT-1999-01093.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Present address:
Inst. de Pharmacologie et Biologie Structurale, UMR 5089 (UPS/CNRS), 205 route de Narbonne, 31077 Toulouse Cedex, France. Tel.:
33-5-61-17-58-45; Fax: 33-5-61-17-59-94; E-mail:
guilhot@ipbs.fr.
This article has been cited by other articles:
![]() |
A. L. Davidson, E. Dassa, C. Orelle, and J. Chen Structure, Function, and Evolution of Bacterial ATP-Binding Cassette Systems Microbiol. Mol. Biol. Rev., June 1, 2008; 72(2): 317 - 364. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Malaga, P. Constant, D. Euphrasie, A. Cataldi, M. Daffe, J.-M. Reyrat, and C. Guilhot Deciphering the Genetic Bases of the Structural Diversity of Phenolic Glycolipids in Strains of the Mycobacterium tuberculosis Complex J. Biol. Chem., May 30, 2008; 283(22): 15177 - 15184. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Hoffmann, A. Leis, M. Niederweis, J. M. Plitzko, and H. Engelhardt Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure PNAS, March 11, 2008; 105(10): 3963 - 3967. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Fontan, V. Aris, S. Ghanny, P. Soteropoulos, and I. Smith Global Transcriptional Profile of Mycobacterium tuberculosis during THP-1 Human Macrophage Infection Infect. Immun., February 1, 2008; 76(2): 717 - 725. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Cantrell, L. Pascopella, J. Flood, C. M. Crane, L. V. Kendall, and L. W. Riley Community-wide transmission of a strain of Mycobacterium tuberculosis that causes reduced lung pathology in mice J. Med. Microbiol., January 1, 2008; 57(1): 21 - 27. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Golby, K. A. Hatch, J. Bacon, R. Cooney, P. Riley, J. Allnutt, J. Hinds, J. Nunez, P. D. Marsh, R. G. Hewinson, et al. Comparative transcriptomics reveals key gene expression differences between the human and bovine pathogens of the Mycobacterium tuberculosis complex Microbiology, October 1, 2007; 153(10): 3323 - 3336. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Simeone, P. Constant, C. Guilhot, M. Daffe, and C. Chalut Identification of the Missing trans-Acting Enoyl Reductase Required for Phthiocerol Dimycocerosate and Phenolglycolipid Biosynthesis in Mycobacterium tuberculosis J. Bacteriol., July 1, 2007; 189(13): 4597 - 4602. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Wolschendorf, M. Mahfoud, and M. Niederweis Porins Are Required for Uptake of Phosphates by Mycobacterium smegmatis J. Bacteriol., March 15, 2007; 189(6): 2435 - 2442. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Raman, X. Puyang, T.-Y. Cheng, D. C. Young, D. B. Moody, and R. N. Husson Mycobacterium tuberculosis SigM Positively Regulates Esx Secreted Protein and Nonribosomal Peptide Synthetase Genes and Down Regulates Virulence-Associated Surface Lipid Synthesis J. Bacteriol., December 15, 2006; 188(24): 8460 - 8468. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. L. Cosma, K. Klein, R. Kim, D. Beery, and L. Ramakrishnan Mycobacterium marinum Erp Is a Virulence Determinant Required for Cell Wall Integrity and Intracellular Survival. Infect. Immun., June 1, 2006; 74(6): 3125 - 3133. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Dainese, S. Rodrigue, G. Delogu, R. Provvedi, L. Laflamme, R. Brzezinski, G. Fadda, I. Smith, L. Gaudreau, G. Palu, et al. Posttranslational Regulation of Mycobacterium tuberculosis Extracytoplasmic-Function Sigma Factor {sigma}L and Roles in Virulence and in Global Regulation of Gene Expression Infect. Immun., April 1, 2006; 74(4): 2457 - 2461. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Mahfoud, S. Sukumaran, P. Hulsmann, K. Grieger, and M. Niederweis Topology of the Porin MspA in the Outer Membrane of Mycobacterium smegmatis J. Biol. Chem., March 3, 2006; 281(9): 5908 - 5915. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Gago, D. Kurth, L. Diacovich, S.-C. Tsai, and H. Gramajo Biochemical and Structural Characterization of an Essential Acyl Coenzyme A Carboxylase from Mycobacterium tuberculosis J. Bacteriol., January 15, 2006; 188(2): 477 - 486. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Stadthagen, J. Kordulakova, R. Griffin, P. Constant, I. Bottova, N. Barilone, B. Gicquel, M. Daffe, and M. Jackson p-Hydroxybenzoic Acid Synthesis in Mycobacterium tuberculosis J. Biol. Chem., December 9, 2005; 280(49): 40699 - 40706. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Pasca, P. Guglierame, E. De Rossi, F. Zara, and G. Riccardi mmpL7 Gene of Mycobacterium tuberculosis Is Responsible for Isoniazid Efflux in Mycobacterium smegmatis Antimicrob. Agents Chemother., November 1, 2005; 49(11): 4775 - 4777. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Deshayes, F. Laval, H. Montrozier, M. Daffe, G. Etienne, and J.-M. Reyrat A Glycosyltransferase Involved in Biosynthesis of Triglycosylated Glycopeptidolipids in Mycobacterium smegmatis: Impact on Surface Properties J. Bacteriol., November 1, 2005; 187(21): 7283 - 7291. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Singh, R. Gupta, R. A. Vishwakarma, P. R. Narayanan, C. N. Paramasivan, V. D. Ramanathan, and A. K. Tyagi Requirement of the mymA Operon for Appropriate Cell Wall Ultrastructure and Persistence of Mycobacterium tuberculosis in the Spleens of Guinea Pigs J. Bacteriol., June 15, 2005; 187(12): 4173 - 4186. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Domenech, M. B. Reed, and C. E. Barry III Contribution of the Mycobacterium tuberculosis MmpL Protein Family to Virulence and Drug Resistance Infect. Immun., June 1, 2005; 73(6): 3492 - 3501. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Serizawa and J. Sekiguchi The Bacillus subtilis YdfHI two-component system regulates the transcription of ydfJ, a member of the RND superfamily Microbiology, June 1, 2005; 151(6): 1769 - 1778. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Etienne, F. Laval, C. Villeneuve, P. Dinadayala, A. Abouwarda, D. Zerbib, A. Galamba, and M. Daffe The cell envelope structure and properties of Mycobacterium smegmatis mc2155: is there a clue for the unique transformability of the strain? Microbiology, June 1, 2005; 151(6): 2075 - 2086. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Lamichhane, S. Tyagi, and W. R. Bishai Designer Arrays for Defined Mutant Analysis To Detect Genes Essential for Survival of Mycobacterium tuberculosis in Mouse Lungs Infect. Immun., April 1, 2005; 73(4): 2533 - 2540. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. S. Hotter, B. J. Wards, P. Mouat, G. S. Besra, J. Gomes, M. Singh, S. Bassett, P. Kawakami, P. R. Wheeler, G. W. de Lisle, et al. Transposon Mutagenesis of Mb0100 at the ppe1-nrp Locus in Mycobacterium bovis Disrupts Phthiocerol Dimycocerosate (PDIM) and Glycosylphenol-PDIM Biosynthesis, Producing an Avirulent Strain with Vaccine Properties At Least Equal to Those of M. bovis BCG J. Bacteriol., April 1, 2005; 187(7): 2267 - 2277. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Dahl, K. Arora, H. I. Boshoff, D. C. Whiteford, S. A. Pacheco, O. J. Walsh, D. Lau-Bonilla, W. B. Davis, and A. G. Garza The relA Homolog of Mycobacterium smegmatis Affects Cell Appearance, Viability, and Gene Expression J. Bacteriol., April 1, 2005; 187(7): 2439 - 2447. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. M. Harvat, Y.-M. Zhang, C. V. Tran, Z. Zhang, M. W. Frank, C. O. Rock, and M. H. Saier Jr. Lysophospholipid Flipping across the Escherichia coli Inner Membrane Catalyzed by a Transporter (LplT) Belonging to the Major Facilitator Superfamily J. Biol. Chem., March 25, 2005; 280(12): 12028 - 12034. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Flores, L. M. Parsons, and M. S. Pavelka Jr. Characterization of Novel Mycobacterium tuberculosis and Mycobacterium smegmatis Mutants Hypersusceptible to {beta}-Lactam Antibiotics J. Bacteriol., March 15, 2005; 187(6): 1892 - 1900. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Portevin, C. de Sousa-D'Auria, H. Montrozier, C. Houssin, A. Stella, M.-A. Laneelle, F. Bardou, C. Guilhot, and M. Daffe The Acyl-AMP Ligase FadD32 and AccD4-containing Acyl-CoA Carboxylase Are Required for the Synthesis of Mycolic Acids and Essential for Mycobacterial Growth: IDENTIFICATION OF THE CARBOXYLATION PRODUCT AND DETERMINATION OF THE ACYL-CoA CARBOXYLASE COMPONENTS J. Biol. Chem., March 11, 2005; 280(10): 8862 - 8874. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Rao, N. Fujiwara, S. A. Porcelli, and M. S. Glickman Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule J. Exp. Med., February 22, 2005; 201(4): 535 - 543. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Perez, P. Constant, A. Lemassu, F. Laval, M. Daffe, and C. Guilhot Characterization of Three Glycosyltransferases Involved in the Biosynthesis of the Phenolic Glycolipid Antigens from the Mycobacterium tuberculosis Complex J. Biol. Chem., October 8, 2004; 279(41): 42574 - 42583. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Perez, P. Constant, F. Laval, A. Lemassu, M.-A. Laneelle, M. Daffe, and C. Guilhot Molecular Dissection of the Role of Two Methyltransferases in the Biosynthesis of Phenolglycolipids and Phthiocerol Dimycoserosate in the Mycobacterium tuberculosis Complex J. Biol. Chem., October 8, 2004; 279(41): 42584 - 42592. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. Philalay, C. O. Palermo, K. A. Hauge, T. R. Rustad, and G. A. Cangelosi Genes Required for Intrinsic Multidrug Resistance in Mycobacterium avium Antimicrob. Agents Chemother., September 1, 2004; 48(9): 3412 - 3418. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Pinto, Q. X. Tang, W. J. Britton, T. S. Leyh, and J. A. Triccas The Mycobacterium tuberculosis cysD and cysNC genes form a stress-induced operon that encodes a tri-functional sulfate-activating complex Microbiology, June 1, 2004; 150(6): 1681 - 1686. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Domenech, M. B. Reed, C. S. Dowd, C. Manca, G. Kaplan, and C. E. Barry III The Role of MmpL8 in Sulfatide Biogenesis and Virulence of Mycobacterium tuberculosis J. Biol. Chem., May 14, 2004; 279(20): 21257 - 21265. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Kocincova, B. Sonden, Y. Bordat, E. Pivert, L. de Mendonca-Lima, B. Gicquel, and J.-M. Reyrat The Hydrophobic Domain of the Mycobacterial Erp Protein Is Not Essential for the Virulence of Mycobacterium tuberculosis Infect. Immun., April 1, 2004; 72(4): 2379 - 2382. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. C. Onwueme, J. A. Ferreras, J. Buglino, C. D. Lima, and L. E. N. Quadri Mycobacterial polyketide-associated proteins are acyltransferases: Proof of principle with Mycobacterium tuberculosis PapA5 PNAS, March 30, 2004; 101(13): 4608 - 4613. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Schnappinger, S. Ehrt, M. I. Voskuil, Y. Liu, J. A. Mangan, I. M. Monahan, G. Dolganov, B. Efron, P. D. Butcher, C. Nathan, et al. Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment J. Exp. Med., September 2, 2003; 198(5): 693 - 704. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. S. Dubey, T. D. Sirakova, M. H. Cynamon, and P. E. Kolattukudy Biochemical Function of msl5 (pks8 plus pks17) in Mycobacterium tuberculosis H37Rv: Biosynthesis of Monomethyl Branched Unsaturated Fatty Acids J. Bacteriol., August 1, 2003; 185(15): 4620 - 4625. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Smith Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence Clin. Microbiol. Rev., July 1, 2003; 16(3): 463 - 496. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. D. Sirakova, V. S. Dubey, H.-J. Kim, M. H. Cynamon, and P. E. Kolattukudy The Largest Open Reading Frame (pks12) in the Mycobacterium tuberculosis Genome Is Involved in Pathogenesis and Dimycocerosyl Phthiocerol Synthesis Infect. Immun., July 1, 2003; 71(7): 3794 - 3801. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Rousseau, T. D. Sirakova, V. S. Dubey, Y. Bordat, P. E. Kolattukudy, B. Gicquel, and M. Jackson Virulence attenuation of two Mas-like polyketide synthase mutants of Mycobacterium tuberculosis Microbiology, July 1, 2003; 149(7): 1837 - 1847. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Lamichhane, M. Zignol, N. J. Blades, D. E. Geiman, A. Dougherty, J. Grosset, K. W. Broman, and W. R. Bishai A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: Application to Mycobacterium tuberculosis PNAS, June 10, 2003; 100(12): 7213 - 7218. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Converse, J. D. Mougous, M. D. Leavell, J. A. Leary, C. R. Bertozzi, and J. S. Cox MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence PNAS, May 13, 2003; 100(10): 6121 - 6126. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Parish, D. A. Smith, S. Kendall, N. Casali, G. J. Bancroft, and N. G. Stoker Deletion of Two-Component Regulatory Systems Increases the Virulence of Mycobacterium tuberculosis Infect. Immun., March 1, 2003; 71(3): 1134 - 1140. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Constant, E. Perez, W. Malaga, M.-A. Laneelle, O. Saurel, M. Daffe, and C. Guilhot Role of the pks15/1 Gene in the Biosynthesis of Phenolglycolipids in the Mycobacterium tuberculosis Complex. EVIDENCE THAT ALL STRAINS SYNTHESIZE GLYCOSYLATED p-HYDROXYBENZOIC METHYL ESTERS AND THAT STRAINS DEVOID OF PHENOLGLYCOLIPIDS HARBOR A FRAMESHIFT MUTATION IN THE pks15/1 GENE J. Biol. Chem., October 4, 2002; 277(41): 38148 - 38158. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Etienne, C. Villeneuve, H. Billman-Jacobe, C. Astarie-Dequeker, M.-A. Dupont, and M. Daffe The impact of the absence of glycopeptidolipids on the ultrastructure, cell surface and cell wall properties, and phagocytosis of Mycobacterium smegmatis Microbiology, October 1, 2002; 148(10): 3089 - 3100. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Kremer, Y. Guerardel, S. S. Gurcha, C. Locht, and G. S. Besra Temperature-induced changes in the cell-wall components of Mycobacterium thermoresistibile Microbiology, October 1, 2002; 148(10): 3145 - 3154. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |